In 1791, Galvani established that electricity activated excitable cells. In the two centuries
that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive
method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins
breakthrough technologies like implantable cardiac pacemakers that we currently take for granted.
However, the contact dependence, and field stimulation that electrical depolarization delivers brings
inherent limitations to the scope and experimental scale that can be achieved. Many of these were not
exposed until reliable in vitro stem-cell derived experimental materials, with genotypes of interest,
were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies)
or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular
constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of
classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools
which put electrically excitable cells under the control of light. We discuss how this enables studies in
cardiac material from the single cell to the whole heart scale. We review the current commercial platforms
that incorporate optogenetic stimulation strategies, and summarize the global literature to date
on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant
to iPS-CM based screening include independence from contact, elimination of electrical stimulation
artefacts in field potential measuring approaches such as the multi-electrode array, and the ability
to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.
Could Frequency-Specific Coupling between Single-Cell Activity and the Local Field Potential Underlie Memory Encoding in the Hippocampus?